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Phase Change MaterialsDave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
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ABSTRACT:
Phase change materials (PCMs) allow the storage of large amounts of latent heat during phase transition. They have the potential to both increase the efficiency of renewable energies such as solar power through storage of excess energy, and to reduce overall energy demand through passive thermal regulation. NASA has identified more than a hundred of these materials. In addition to passive energy storage, they have application in thermo-regulated fabrics, high power electronics, telecommunication installations and microprocessors. PCMs are not suitable for use without prior encapsulation. Encapsulation in a shell material provides benefits including protection of the PCM from the external environment and increased specific surface area to improve heat transfer. | ||||||
Synthesis and Fabrication of Surface-Active Microparticles Using a Membrane Emulsion Technique and Conjugation of Model Protein via Strain-Promoted Azide–Alkyne Click Chemistry in Physiological Conditions |
ABSTRACT:
The rapid surface immobilization of protein on monodispersed polyester microcarriers is reported. A model protein, functionalized with a dibenzocyclooctyne core, immobilizes on the surface of azide-terminal polycaprolactone microcarriers within 10 min compared to 12 h for other conjugation techniques, and it is conducted in physiological conditions and in the absence of coupling reagents. Grace Walden, Xin Liao, Graham Riley, Simon Donell, Michael J. Raxworthy, and Aram Saeed
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Liposomes & Lipid nanoparticlesDave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
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ABSTRACT:
Since their discovery in 1965, by Alec D. Bangham, liposomes have been recognised as the drug delivery vehicle of choice. Their biocompatibility results in minimal adverse reactions. Their amphiphilic structure allows encapsulation of both hydrophilic and hydrophobic active pharmaceutical ingredients (APIs). More recently the liposome’s analogous cousin, the lipid nanoparticle, has gained prominence because of its ability to deliver therapeutic payloads, including DNA and mRNA for vaccines. They can both deliver their payload very precisely through treating their surface with proteins allowing highly specific binding to a target cell type. This paper describes the advantages, over the most common commercial processes, that Micropore's membrane emulsification technology has in Liposomes and Lipid nanoparticle production. | ||||||
Sustained release PLGA microspheres.Dave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
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ABSTRACT:
Commercialisation of sustained release formulations began in the 1970s with PLA & PGA used for surgical implants and sutures. PLGA (Poly (lactic acid-co-glycolic acid)) quickly emerged as the most important biocompatible, non-toxic polymer with numerous applications in drug delivery, tissue engineering, medical and surgical devices. PLGA is approved worldwide for several therapeutic applications because of its biodegradability, biocompatibility and sustained-release properties. Despite this longevity, PLGA is not easy to formulate into sustained release drug products with the result that inventor drug products and generic versions remain scarce with only 20 drugs approved in 30+ years. Aseptic membrane emulsification devices can now be used to form PLGA microspheres from lab scale to full scale manufacturing using the well-proven solvent evaporation method of production. | ||||||
Hydrogels in drug delivery & biomedical engineeringDave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
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ABSTRACT:
Hydrogels consist of three-dimensional, hydrophilic, polymeric networks capable of holding large quantities of solvated hydrophilic drugs. Since the early 1960s they have been considered for controlled release of trapped drugs, both small molecule and macromolecular drugs, through slow diffusion. They possess tuneable properties and the capability to protect labile drugs from degradation controlling their release. Their resemblance to living tissue opens up many opportunities for biomedical applications. Currently, hydrogels are used for manufacturing contact lenses, hygiene products, wound dressings, tissue engineering scaffolds and drug delivery systems. Membrane emulsification sidesteps the challenges of creating hydrogels by forming droplets directly as a w/o emulsion with precise size control forming perfectly spherical droplets in sizes less than 50µm. | ||||||
Core-shell coacervation in drug deliveryDave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
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ABSTRACT:
The term coacervation derives from the Latin verb “coacervare”, meaning “to crowd together”. The technique of coacervation was first characterised by Bungenberg de Jong in 1931, although the earliest reports of this technique go back to Tiebackx in 1911. Over the last 2-3 decades complex coacervation has been deployed in industries as diverse as food, cosmetics, agriculture and functional materials, as well as, more recently, generating an increasing interest in the pharmaceutical industry as a drug delivery mechanism. This White Paper focuses on drug delivery using complex coacervation. Achieving an accurate target capsule size in an industrial setting can be a challenge While the homogeniser is running, samples are taken and sized via electrozone sensing (Coulter principle) or laser diffraction. These techniques take time to run, and in the meantime the homogeniser continues to reduce the size of the emulsion droplets in the batch. This makes accurate sizing unpredictable.A preferred approach is a system where the desired size characteristics can be defined in advance and the emulsion produced in a single pass. Membrane emulsification makes this possible, by injecting the internal phase through the membrane pores and, by applying a known shear force, droplet sizes can be controlled precisely. | ||||||
Silica particles.Dave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
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ABSTRACT:
Mesoporous silica particles (MSP) have gained wide popularity over recent years. Their advantages of uniform and tunable pore size, easy independent functionalization of the surface, internal and external pores and the gating mechanism of the pore opening make it a distinctive drug carrier. The unique feature of MSPs which makes them a widely exploited carrier for drug delivery is its high loading capacity due to the large pore volume and surface engineering properties both on the external and internal surface for better drug targeting. These versatile carriers can be used for loading a variety of cargos ranging from drugs to macromolecules such as proteins, DNA and RNA. Through an improved, continuous, scalable sol-gel process both micro- and mesoporous near-monodispersed spherical particles can be produced in large continuous volumes using aseptic membrane emulsification devices with a range of internal pores between 1 and 12nm and an average surface area between 300 and 750 m2g-1. | ||||||
API CrystallisationDave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
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ABSTRACT:
The ability to deliver a drug to a patient in a safe, efficacious and cost-effective manner most commonly depends on the physicochemical properties of the active pharmaceutical ingredient (API) in the solid state. In this context, crystallisation is of critical importance in pharmaceutical industry as it defines physical and powder properties of crystalline APIs. Detailed knowledge of the various aspects of crystallisation process, and in particular, an understanding of the relationships between crystallisation, solid-state form and properties is required to deliver the desired therapeutic effect and to avoid undesirable effects. Membrane crystallisation is a relatively new technique based on the use of a porous material as a semi-permeable barrier between two phases. The membrane can be used to create supersaturation by solvent evaporation, antisolvent or reactant addition, and mixing with a colder solvent . The first membrane crystallisation process dates back to 1917 but recently, membranes have been used to crystallize proteins and macromolecules. The presence of a membrane adds a supplementary resistance to mass transfer, but it also offers additional control over nucleation kinetics. | ||||||
Monodisperse Liquid Foams via Membrane FoamingLaura Carballido, Miriam Dabrowski, Friederike Dehli, Lukas Koch, Cosima Stubenrauch*
Institute of Physical Chemistry Pfaffenwaldring 55, 70569 Stuttgart, Germany *cosima.stubenrauch@ipc.uni-stuttgart.de, 0049 711 685-64470
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ABSTRACT:
Hypothesis It is possible to generate fairly monodisperse liquid foams by a dispersion cell, which was originally designed for the generation of fairly monodisperse emulsions. If this is the case, scaling-up the production of monodisperse liquid and solid foams will be no longer a problem. Experiments We used the dispersion cell - a batch process - and examined the influence of stirrer speed, membrane pore diameter and injection rate on the structure of the resulting liquid foams. We used an aqueous surfactant solution as scouting system. Once the experimental conditions were known we generated gelatin-based liquid foams and methacrylate-based foamed emulsions. Findings We found that (a) the bubble size of the generated liquid foams can be adjusted by varying the membrane pore diameter, (b) no stirrer should be used to obtain monodisperse foams, and (c) the bubble size is not influenced by the air injection rate. Since (i) the output for all investigated systems is up to two orders of magnitude larger compared to microfluidics and (ii) the membrane technology can very easily be scaled-up if run in a continuous process, the use of membrane foaming is expected to be heavily used for the generation of monodisperse liquid and solid foams, respectively. | ||||||
Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG- ε-caprolactone) ‑b‑Poly (L‑lactide) Multiblock Copolymer MicrospheresKarina C. Scheiner,† Roel F. Maas-Bakker,† Thanh T. Nguyen,‡ Ana M. Duarte,‡ Gert Hendriks,‡
Lídia Sequeira,‡ Garry P. Duffy,§ Rob Steendam,‡ Wim E. Hennink,† and Robbert J. Kok*,† †Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands ‡InnoCore Pharmaceuticals B.V., L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands §Discipline of Anatomy, School of Medicine, National University of Ireland Galway, University Road, H91 TK33 Galway, Ireland 
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ABSTRACT:
Vascular endothelial growth factor (VEGF) is the major regulating factor for the formation of new blood vessels, also known as angiogenesis. VEGF is often incorporated in synthetic scaffolds to promote vascularization and to enhance the survival of cells that have been seeded in these devices. Such applications require sustained local delivery of VEGF of around 4 weeks for stable blood vessel formation. Most delivery systems for VEGF only provide short-term release for a couple of days, followed by a release phase with very low VEGF release. We now have developed VEGF-loaded polymeric microspheres that provide sustained release of bioactive VEGF for 4 weeks. Blends of two swellable poly(ε-caprolactone)−poly(ethylene glycol)−poly(ε-caprolactone)-b-poly(L-lactide) ([PCL−PEG−PCL]-b-[PLLA])-based multiblock copolymers with different PEG content and PEG molecular weight were used to prepare the microspheres. Loading of the microspheres was established by a solvent evaporation-based membrane emulsification method. The resulting VEGF-loaded microspheres had average sizes of 40−50 μm and a narrow size distribution. Optimized formulations of a 50:50 blend of the two multiblock copolymers had an average VEGF loading of 0.79 ± 0.09%, representing a high average VEGF loading efficiency of 78 ± 16%. These microspheres released VEGF continuously over 4 weeks in phosphate-buffered saline pH 7.4 at 37 °C. This release profile was preserved after repeated and long-term storage at −20 °C for up to 9 months, thereby demonstrating excellent storage stability. VEGF release was governed by diffusion through the water-filled polymer matrix, depending on PEG molecular weight and PEG content of the polymers. The bioactivity of the released VEGF was retained within the experimental error in the 4-week release window, as demonstrated using a human umbilical vein endothelial cells proliferation assay. Thus, the microspheres prepared in this study are suitable for embedment in polymeric scaffolds with the aim of promoting their functional vascularization. | ||||||
Generation of magnesium enriched water-in-oil-in-water food emulsions by stirred cell membrane emulsification Xiaolu Pu, Bettina Wolf, Marijana Dragosavac Journal of Food Engineering
Volume 247, April 2019, Pages 178-187 |
ABSTRACT: This study has for the first time shown that complex food emulsifiers such as starch and protein can be applied to produce stable w/o/w emulsions with the membrane emulsification technology. Using a microporous metal membrane with a 20 μm pore size, 2% of polyoxyethylene (20) sorbitan monolaurate (Tween 20), 4% of octenyl succinic anhydride (OSA) starch or 1.5% of pea protein isolate (PPI) in the external water phase respectively was the minimum concentration necessary to stabilise the w/o/w droplets. Uniform with a span as low as 0.45 and for at least 13-day stable w/o/w emulsions of droplets between 35 and 320 μm were obtained. The release of a magnesium tracer from the internal water phase of xanthan gum-thickened w/o/w emulsions, when OSA starch and PPI were used, was found to be limited to around 3% after 13-day storage. However, w/o/w emulsions stabilised with Tween 20 were less stable with magnesium showing a release of 27% on day 13.
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Dynamic Aroma Release from Complex Food EmulsionsXiaolu Pu, Robert Linforth,M. M. Dragosavac, and Bettina Wolf
J. Agric. Food Chem.2019 |
ABSTRACT: In-vitro dynamic aroma release over oil-in-water (o/w) and water-in-oil-in-water (w/o/w) emulsions stabilised with Tween 20 or octenyl succinic anhydride (OSA) starch as a hydrophilic emulsifier and polyglycerol polyricinoleate (PGPR) as a hydrophobic emulsifier was investigated. The equal-molecular-weight hydrophilic aroma diacetyl (2,3-butanedione) or relatively-more-hydrophobic 3-pentanone was added to the emulsions prepared by high speed mixing, or membrane emulsification followed by thickened with xanthan gum removing droplet size distribution and creaming as variables affecting dynamic release. Results showed the differences of w/o/w emulsions in the dynamic release compared to o/w emulsions mainly depended on aroma hydrophobicity, emulsion type, emulsifier-aroma interactions and creaming. Xanthan led to a reduced headspace replenishment. Interfacially adsorbed OSA starch and xanthan-OSA starch interaction influenced diacetyl release over emulsions. OSA starch alone interacted with 3-pentanone. This study demonstrates the potential impact of emulsifying and thickening systems on aroma release systems and highlights that specific interactions may compromise product quality.
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Uniform polymer beads by membrane emulsification-assisted suspension polymerisationAuthors: M. Alroaithi and S. Sajjadi
Further ref: RSC Adv., 2016, 6, 79745 |
ABSTRACT: This work focuses on a two-stage polymerisation process for the production of uniform polymer beads. Highly uniform droplets were firstly produced by a stirred-vessel membrane emulsification device. Methyl methacrylate (MMA) and a specific grade of polyvinyl alcohol (PVA) were used as monomer and stabiliser, respectively. The effects of various process parameters affecting the droplet size and uniformity including feeding policy, agitation speed, stabiliser concentration, and flowrate were investigated. The evolution of droplet size and its coefficient of variation (CV) were monitored over the course of emulsification. A new start-up policy, validated by monitoring droplet formation at the membrane surface, was introduced that eliminated the non-uniformity in the size of droplets formed early during emulsification. The mechanisms contributing to droplet size distribution broadening at the membrane surface during formation were decoupled from those acting in the emulsification vessel during circulation. The high CV obtained at low PVA concentration and high agitation speed was attributed to drop breakup and coalescence occurring in the emulsification vessel, respectively, after droplets formed. The emulsification was followed by a shear-controlled suspension polymerisation to convert the discrete droplets of monomer to polymer beads. A wide range of reactor impeller speeds and PVA concentrations was studied to find the conditions under which the droplets formed via membrane emulsification would not undergo further break-up or coalesce during polymerisations and a one-to-one copy of the initial droplets with the same CV can be achieved
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Controlled multiphase oxidations for continuous manufacturing of fine chemicalsAuthors: K. N. Loponova, B. J. Deadman, J. Zhu, C. Rielly, R. G. Holdich, K. K. Hii, K. Hellgardt
Further ref: Chemical Engineering Journal, Volume 329, 1 December 2017, Pages 220-230 |
ABSTRACT: The feasibility of an integrated continuous biphasic oxidation process was studied, incorporating (i) electrochemical generation of an oxidant, (ii) membrane emulsification and an Oscillatory Flow Reactor (OFR) to facilitate mass-transfer in a biphasic reaction system and (iii) product extraction to enable regeneration of the oxidant. The biphasic, organic solvent-free dihydroxylation of styrene by ammonium peroxodisulfate solutions (including electrochemically generated peroxodisulfate) was investigated as a model reaction, both in batch and in an OFR. Heating of peroxodisulfate in a strongly acidic solution was demonstrated to be essential to generate the active oxidant (Caro’s acid). Membrane emulsification allowed mass-transfer limitations to be overcome, reducing the time scale of styrene oxidation from several hours in a conventional stirred tank reactor to less than 50 min in a dispersion cell. The influence of droplet size on overall reaction rate in emulsions was studied in detail using fast image capturing technology. Generation of unstable emulsions was also demonstrated during the oxidation in OFR and product yields >70% were obtained. However, the high-frequency/high-displacement oscillations necessary for generation of fine droplets violated the plug flow regime. Membrane emulsification was successfully integrated with the OFR to perform biphasic oxidations. It was possible to operate the OFR/cross-flow membrane assembly in plug flow regime at some oscillatory conditions with comparable overall oxidation rates. No mass-transfer limitations were observed for droplets <60 μm. Finally, the continuous post-reaction separation was demonstrated in a single OFR extraction unit to enable continuous regeneration of the oxidant
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Concentrated Pickering Emulsions with Narrow Size Distributions using Stirred Cell Membrane EmulsificationAuthors: M. S. Manga and D. W. York
Further ref: Langmuir, 2017, 33, 36, 9050-9056 |
ABSTRACT: Stirred cell membrane emulsification (SCME) has been employed to prepare concentrated Pickering oil in water emulsions solely stabilized by fumed silica nanoparticles. The optimal conditions under which highly stable and low polydispersity concentrated emulsions using the SCME approach are highlighted. Optimization of the oil flux rates and the paddle stirrer speeds are critical to achieving control over the droplet size and size distribution. Investigating the influence of oil volume fraction highlights the criticality of the initial particle loading in the continuous phase on the final droplet size and polydispersity. At a particle loading of 4 wt%, both the droplet size and polydispersity increase with increasing of the oil volume fraction above 50%. As more interfacial area is produced the number of particles available in the continuous phase diminish and coincidently a reduction in the kinetics of particle adsorption to the interface resulting in larger polydisperse droplets. Increasing the particle loading to 10 wt%, leads to significant improvements in both size and polydispersity with oil volume fractions as high as 70% produced with coefficient of variation values as low as ~30% compared to ~75% using conventional homogenization techniques.
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Membrane emulsification: Formation of water in oil emulsions using a hydrophilic membraneAuthors: P. S. Silva, V. M. Starov, R. G. Holdich
Further ref: Colloids Surf. A., Volume 532, 5 November 2017, Pages 297-304 |
ABSTRACT: It is shown that formation of water based droplets in an immiscible (i.e. oil) continuous phase can be achieved using a hydrophilic porous metal membrane without prior hydrophobic treatment of the membrane surface. This avoids the need for “health and safety approval” of typical hydrophobic treatments for the membrane, which often use chemicals incompatible with pharma or food applications. To investigate this, wetting experiments were carried out: sessile droplets were used to determine static contact angles and a rotating drum system was used to determine contact angles under dynamic conditions. In the latter case the three-phase contact line was observed between the rotating drum, water and the continuous phase used in the emulsification process; a surfactant was present in the continuous phase which, in this process, has a double function: to assist the wetting of the membrane by the continuous phase, and not the disperse phase, and to stabilize the droplets formed at the surface of the porous membrane during membrane emulsification.
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Encapsulation and controlled release of rapamycin from polycaprolactone nanoparticles prepared by membrane micromixing combined with antisolvent precipitationAuthors: R. Othman, G. T. Vladisavljevic, Z. K. Nagy, and R. G. Holdich
Further ref: Langmuir 2016, 32, 41, 10685-10693 |
ABSTRACT: Rapamycin-loaded polycaprolactone nanoparticles (RAPA-PCL NPs) with a polydispersity index of 0.006–0.073 were fabricated by antisolvent precipitation combined with micromixing using a ringed stainless steel membrane with 10 μm diameter laser-drilled pores. The organic phase composed of 6 g L–1 PCL and 0.6–3.0 g L–1 RAPA in acetone was injected through the membrane at 140 L m–2 h–1 into 0.2 wt % aqueous poly(vinyl alcohol) solution stirred at 1300 rpm, resulting in a Z-average mean of 189–218 nm, a drug encapsulation efficiency of 98.8–98.9%, and a drug loading in the NPs of 9–33%. The encapsulation of RAPA was confirmed by UV–vis spectroscopy, XRD, DSC, and ATR-FTIR. The disappearance of sharp characteristic peaks of crystalline RAPA in the XRD pattern of RAPA-PCL NPs revealed that the drug was molecularly dispersed in the polymer matrix or RAPA and PCL were present in individual amorphous domains. The rate of drug release in pure water was negligible due to low aqueous solubility of RAPA. RAPA-PCL NPs released more than 91% of their drug cargo after 2.5 h in the release medium composed of 0.78–1.5 M of the hydrotropic agent N,N-diethylnicotinamide, 10 vol % ethanol, and 2 vol % Tween 20 in phosphate buffered saline. The dissolution of RAPA was slower when the drug was embedded in the PCL matrix of the NPs than dispersed in the form of pure RAPA nanocrystals.
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Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion DevicesAuthors: Y. Lu, D. Chowdhury, G. T. Vladisavljević, K. Koutroumanis and S. Georgiadou
Further ref: Membranes 2016, 6(2), 29 |
ABSTRACT: Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF) or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.
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Structure and Mechanical Properties of Consumer-Friendly PMMA MicrocapsulesAuthors: X. Pan, R. Mercadé-Prieto, D. York, J. A. Preece, and Z. Zhang
Further ref: Ind. Eng. Chem. Res. 2013, 52, 11253−11265 |
ABSTRACT: Environmentally and consumer-friendly poly(methyl methacrylate) (PMMA) microcapsules were prepared on the basis of an in situ polymerization reaction to encapsulate perfume oil, which aims to be delivered to fabric surfaces via liquid detergents. Microcapsules with a narrow size distribution were produced using a membrane emulsification system; results were compared with a standard homogenization procedure. The shell thickness of microcapsules was found to increase with the polymerization reaction time, which was measured using a lipophilic fluorescent dye dissolved in the perfume oil and confocal laser scanning microscopy. Microcapsules with a wide range of shell thicknesses could be produced by modifying the reaction time. The force versus displacement profiles obtained from compression of single such microcapsules between two parallel surfaces based on micromanipulation were very different: thin-shell microcapsules burst under compression, whereas thick-shell microcapsules did not. However, the intrinsic mechanical properties of the PMMA shells, determined with finite element modeling (FEM) and the experimental data, such as the elastic modulus and the rupture stress, were found independent of the reaction time. The microcapsules with a wide range of shell thicknesses may be used to encapsulate different oil-based active ingredients for potential industrial applications.
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Multifactorial Design of Poly(D,L-lactic-co-glycolic acid) Capsules with Various Release Properties for Differently Sized Filling AgentsAuthors: S. Schmitz-Hertzberg, W. C. Mak, K. K. Lai, C. Teller, F. F. Bier
Further ref: . J. Appl. Polym. Sci. 130: 4219–4228, 2013 |
ABSTRACT: The hydrolytic degradation and corresponding content release of capsules made of poly(d,l‐lactic‐co‐glycolic acid) (PLGA) strongly depends on the composition and material properties of the initially applied copolymer. Consecutive or simultaneous release from capsule batches of combinable material compositions, therefore, offers high control over the bioavailability of an encapsulated drug. The keynote of this study was the creation of a superordinated database that addressed the correlation between the release kinetics of filling agents with different molecular weights from PLGA capsules of alternating composition. Fluorescein isothiocyanate (FITC)–dextran (with molecular weights of 4, 40, and 2000 kDa) was chosen as a model analyte, whereas the copolymers were taken from various 50:50 PLGA, 75:25 PLGA, and polylactide blends. With reference to recent publications, the capsule properties, such as the size, morphology, and encapsulation efficiency, were further modified during production. Hence, uniform microdisperse and polydisperse submicrometer nanocapsules were prepared by two different water‐in‐oil‐in‐water emulsification techniques, and additional effects on the size and morphology were achieved by capsule solidification in two different sodium salt buffers. The qualitative and quantitative examination of the physical capsule properties was performed by confocal laser scanning microscopy, scanning electron microscopy, and Coulter counting techniques to evaluate the capsule size distribution and the morphological appearance of the different batches. The corresponding agent release was quantified by fluorescence measurement of the FITC–dextran in the incubation media and by the direct measurement of the capsule brightness via fluorescence microscopy. In summary, the observed agent release showed a highly controllable flexibility depending on the PLGA blends, preparation methods, and molecular weight of the used filling substances
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Size and strength distributions of melamine-formaldehyde microcapsules prepared by membrane emulsification.Authors: X. Pan, D. York, J. A. Preece and Z. Zhang
Further ref: Powder Technology, 2012, 227, 43–50 |
ABSTRACT: Melamine formaldehyde microcapsules containing an oil-based active ingredient were prepared using a flat membrane combined with a mechanical stirrer (also called dispersion cell) to generate oil droplets followed by in situ polymerization of melamine formaldehyde precondensate on their surface. The effects of membrane properties and process conditions on the size and size distribution of the oil droplets produced in the stage of emulsification and the final microcapsules were investigated by a static light scattering (SLS) technique. Besides, the morphology of the microcapsules, their shell thickness and mechanical properties were characterised by optical microscopy, environmental-scanning electron microscopy (ESEM), transmission electron microscopy (TEM), and a micromanipulation technique respectively.
It has been found that the size distribution of the oil droplets or microcapsules, characterised by a value of coefficient of variation (CV) depended on the flux of the dispersed oil phase through the membrane and agitation speed of the stirrer in the dispersion cell. The smallest CV value of the microcapsules prepared by a membrane with a pore size of 15 μm and the distance between pores of 200 μm was 21.0 ± 0.5% at a flux of the dispersed oil phase of 1.5 × 10− 5 m·s− 1 and an agitation speed of 1080 rpm, and the corresponding CV value of the rupture force of the microcapsules was 18.6 ± 0.1%. In comparison with the corresponding data obtained from the microcapsules made using conventional homogenization to generate emulsion droplets (CV value of 34.1 ± 0.3% for diameter and 34.4 ± 0.2% for rupture force), the distributions of the size and mechanical strength of the microcapsules have been significantly narrowed using the membrane emulsion, which clearly demonstrates its advantage. |
Preparation of Pickering Emulsions and Colloidosomes with Relatively Narrow Size Distributions by Stirred Cell Membrane EmulsificationAuthors: K. L. Thompson, S. P. Armes and D. W. York
Further ref: Langmuir, (2011), 27(6), 2357–2363 |
ABSTRACT: Stirred cell membrane emulsification has been used to prepare Pickering emulsions and covalently cross-linked colloidosomes using poly(glycerol monomethacrylate) stabilized polystyrene particles as the sole emulsifier. Pickering emulsions of 44−269 μm in size can be prepared with coefficients of variation as low as 25%, by varying the emulsification parameters. The cell membranes consisted of 5 μm pores with a pore-to-pore spacing of 200 μm. Significantly more uniform emulsions are produced when these open pores are restricted to a narrow ring around the membrane surface. Increasing the oil flux rate through this annular ring membrane increases both the size and polydispersity of the resulting emulsion droplets. There was no evidence for a “push off” force contributing to droplet detachment over the oil flux range investigated. Increasing the paddle stirrer speed from 500 to 1500 rpm reduces the average droplet diameter from 269 to 51 μm while simultaneously decreasing the coefficient of variation from 47% to 25%. Any further increase in surface shear led to droplet breakup within the dispersion cell and resulted in a significantly more polydisperse emulsion. The Pickering emulsions reported here have much narrower droplet size distributions than those prepared in control experiments by conventional homogenization (25% vs 74% coefficients of variation). Finally, low polydispersity colloidosomes can be conveniently prepared by the addition of an oil soluble polymeric cross-linker to the dispersed phase to react with the stabilizer chains.
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Generation of magnesium enriched water-in-oil-in-water food emulsions by stirred cell membrane emulsificationX. Pu, B. Wolf, M. M. Dragosavac
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ABSTRACT: This study has for the first time shown that complex food emulsifiers such as starch and protein can be applied to produce stable w/o/w emulsions with the membrane emulsification technology. Using a microporous metal membrane with a 20 μm pore size, 2% of polyoxyethylene (20) sorbitan monolaurate (Tween 20), 4% of octenyl succinic anhydride (OSA) starch or 1.5% of pea protein isolate (PPI) in the external water phase respectively was the minimum concentration necessary to stabilise the w/o/w droplets. Uniform with a span as low as 0.45 and for at least 13-day stable w/o/w emulsions of droplets between 35 and 320 μm were obtained. The release of a magnesium tracer from the internal water phase of xanthan gum-thickened w/o/w emulsions, when OSA starch and PPI were used, was found to be limited to around 3% after 13-day storage. However, w/o/w emulsions stabilised with Tween 20 were less stable with magnesium showing a release of 27% on day 13.
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Microparticles for cell encapsulation and colonic delivery produced by membrane emulsificationS. Morell, R.G. Holdich, M.M. Dragosavac
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ABSTRACT: Membrane Emulsification was used to encapsulate yeast cells and form microparticles. W/O emulsions were produced using a Dispersion Cell; the aqueous phase consisted of gelatin/chitosan, or pure gelatin solution, containing yeast cells, the continuous phase was 2 wt% of SPAN 80 in kerosene. Varying the dispersed phase flux (from 70 to 350 L h- m-2) and the shear stress (from 17 to 1 Pa) applied on the membrane surface droplet sizes of between 60 and 340 µm were produced, with a coefficient of variation of 17% under the best operating conditions. The liquid drops were loaded with increasing amount of yeast (3.14×107 to 3.14×108 cells/mL). The stability and uniformity of the emulsions was independent of the cell concentration. PTFE coated hydrophobic membrane produced smaller W/O drops compared to FAS coated membranes. The liquid polymeric droplets were solidified in solid particles using thermal gelation and/or ionic crosslinking, obtaining yeast encapsulated particles sized ~100 µm. The pH sensitive polymer, Eudragit S100, was used as a coating to create gastro resistant particles suitable for intestinal-colonic targeted release. Viability of the released yeast cells was demonstrated using fluorescence probes and checking cell glucose metabolism with time.
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Chitosan and Poly (Vinyl Alcohol) microparticles produced by membrane emulsification for encapsulation and pH controlled releaseS. Morell, R.G. Holdich, M.M. Dragosavac
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ABSTRACT: The Dispersion Cell membrane emulsification technique was used for the production of w/o emulsions with controlled droplet size and narrow size distribution. The influence of the operating parameters of the process was investigated. Varying the dispersed phase flux (10–1250 L h−1 m−2) and the shear stress (2–59 Pa), droplets between 30 and 280 μm were produced with CV’s as low as 18%. Nickel and stainless steel membranes were used for the membrane emulsification. Pore geometry influenced the droplet size as well as uniformity and a normally hydrophilic stainless steel membrane with sharp pore openings produced more uniform and smaller drops compared to a PTFE coated hydrophobic nickel membrane with a conical pore surface. For the dispersed phase 15 wt.% PVA or 1–3 wt.% chitosan as well as their blends in water were used. Surfactants PGPR and ABIL EM90 were tested to determine their capability to form stable emulsions in Miglyol 840. PGPR could not be used to stabilize the emulsion with chitosan as the dispersed phase, probably due to the chemical interference between the carboxyl group present in the PGPR and chitosan. Solid microparticles were obtained by chemical crosslinking with glutaraldehyde (GA) at different concentrations (1–50 vol.%). Particles crosslinked using less than 10 vol.% GA were able to swell and release encapsulated compounds. Acid sensitive particles were produced by blending the PVA and chitosan. Up to 80% of Cu2+ and 20% of sodium salicylate was released from the particles under acidic conditions. No significant release was determined under neutral conditions.
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Continuous Production of Cellulose Microbeads via Membrane EmulsificationJames Coombs O’Brien,
Laura Torrente-Murciano, Davide Mattia, Janet L. Scott |
ABSTRACT: We report on the continuous manufacturing of cellulose microbeads as a sustainable alternative to plastic microparticles, currently used in a wide range of consumer products from toothpaste to paints. Plastic microbeads are not retained by, or degraded in, wastewater treatment plants (due to their size and composition), accumulating in the environment in general and aquatic life in particular, eventually finding their way into the human food supply chain. Here, it is demonstrated, for the first time, that a cross-flow membrane emulsification–phase inversion process can be used to generate stabilized microdroplets of cellulose dissolved in an organic electrolyte solution (1-ethyl-3-methylimidazolium acetate:DMSO) in a sunflower oil-Span 80 continuous phase. The emulsion is subsequently coagulated with an antisolvent, resulting in the formation of solid, spherical, and biodegradable cellulose microbeads. A systematic analysis of process parameters (continuous and disperse phase flow rate, viscosity, and applied pressure) allowed the determination of a regime within which microspheres can be predictably produced using a 10 μm pore-sized porous glass membrane. Cross-linking of the cellulose beads with glyoxal led to a 3-fold increase in compressive strength of the beads, broadening the potential range of applications where these biodegradable particles could replace current environmentally persistent materials.
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Development of enzyme-loaded PVA microspheres by membrane emulsificationEmma Piacentini
Mengying Yan Lidietta Giorno |
ABSTRACT: Enzyme applications have a considerable role at the heart of biotechnological processes. A large number of these biotechnological processes require successful enzyme immobilization in terms of resistance to leaking, retention of enzyme activity over long-term storage, operational stability under adverse environmental conditions, accessibility to substrates, fast catalysis, and, in general, proper enzyme immobilization density with adequate orientation. Among the different methods of immobilization, enzyme encapsulation in a network matrix of polymeric materials in the form of particles is of particular interest. Polyvinyl alcohol (PVA) microspheres produced by a membrane emulsification/cross-linking method have been used as enzyme carriers. The enzyme was immobilized during particle formation (by entrapment) or after particle production (by adsorption and cross-linking). The entrapment during particle solidification from a water in oil (W/O) emulsion, allowed the enzyme to be distributed at the interface in its active form. The best operating conditions to control particle size, particle size distribution and particle structure for PVA microspheres production as well as the most suitable method for lipase immobilization on/in PVA microspheres have been identified. The immobilization method that does not affect enzyme intrinsic biocatalytic activity, whilst allowing at the same time confinement with balance between molecular mobility and heterogenization has been identified.
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Semi-continuous production of iron oxide nanoparticles via membrane emulsificationMaria Medina-Llamas
Davide Mattia |
ABSTRACT: The large-scale production of nanomaterials with fine control over their shape, size and properties remains a major obstacle towards their further use. Here, the semi-continuous production of metal oxide nanoparticles (NPs) via membrane emulsification (ME) is reported for the first time, using an oil-in-water emulsion and a commercial stirred ME setup fitted with a novel ring-shaped anodic alumina membrane (AAM). A systematic investigation of process parameters showed that the narrow pore size distribution of AAMs resulted in a narrow size distribution of both droplets and particles, with Ddroplet/Dpore as small as 2.8, compared to typical literature values of 10 or more. The average particle size was 4.2 ± 0.5 nm and 18 ± 4 nm for the as-synthetized and calcined NPs, respectively. Calculations of the emulsion production rate demonstrate the potential of the ME setup to produce up to 1 kg of NP per hour per metre squared of membrane.
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Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore ArraysRahimah Othman*†‡
Goran T. Vladisavljević*† Elena Simone†§ Zoltan K. Nagy†⊥ Richard G. Holdich† |
ABSTRACT: Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7–34 μm and was controlled by the PRX concentration in the feed solution (15–25 g L–1), antisolvent/solvent volume ratio (5–30), and type of antisolvent (Milli-Q water or 0.1–0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L–1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals.
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Production of molecularly imprinted polymer particles with amide-decorated cavities for CO2 capture using membrane emulsification/suspension polymerisationSeyed Ali Nabavi
Goran T. Vladisavljević Agni Wicaksonob Stella Georgiadou Vasilije Manović |
ABSTRACT: Highly uniform amide-based molecularly imprinted polymer (MIP) particles containing CO2-philic cavities decorated with amide groups were produced using membrane emulsification and subsequent suspension polymerisation. The organic phase containing acrylamide (functional monomer), oxalic acid (dummy template), ethylene glycol dimethacrylate (crosslinker) and azobisisobutyronitrile (initiator) dissolved in a 50/50 mixture (by volume) of acetonitrile and toluene (porogenic solvents) was injected through a microengineered nickel membrane with a pore diameter of 20 μm and a pore spacing of 200 μm into agitated 0.5 wt% aqueous solution of poly(vinyl alcohol) to form droplets that have been polymerised at 60 °C for 3 h. The volume median diameter of the droplets was controlled between 35 and 158 μm by shear stress at the membrane surface. The droplets maintained their physical stability during storage for 4 weeks and their size was independent of the dispersed phase content. The particle size after polymerisation was consistent with the initial droplet size. The particles were stable up to 210 °C and had a specific surface area of 239 m2/g and a CO2 capture capacity of 0.59 mmol/g at 273 K and 0.15 bar CO2 partial pressure.
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Rotating Membrane Emulsification for Producing Single and Multiple EmulsionsNita Aryanti1* and Richard A. Williams1
1 Department of Chemical Engineering, Kampus Undip Tembalang, Semarang, 50278 2 Heriot-Watt University, Edinburgh EH14 4AS * Corresponding author: nita.aryanti@che.undip.ac.id Issue: MATEC Web Conf. Volume 156, 2018 The 24th Regional Symposium on Chemical Engineering (RSCE 2017) Article Number 08001 Number of page(s) 5 Section Membrane Science, Material and Technologies DOI Published online 14 March 2018 |
ABSTRACT: Membrane emulsification is a technique utilising a novel concept of generating droplet ‘drop by drop’ to produce emulsions. The technique has several distinctive advantages over the conventional emulsification techniques.This paper concerns on the development of membrane emulsification (Rotating Membrane Reactor, RMR) which utilizes rotating tubular membrane to initiate droplet detachments. The RMR uses a rotating stainless steel tubular membrane with laser drilled pores (100 μm pore diameter) and a syringe pump to drive the dispersed phase through the membrane at a given flow rate. O/W formulations were prepared with low viscosity of paraffin wax, two types of emulsifiers, different membrane rotation rate and dispersed phase flow rate. The emulsion droplets exhibited a coefficient of variation of 9% and 81μm droplet size. In this research, the pore size/droplet size ratio could achieve 0.8. This value was below than other membrane emulsification processes. The effects of principal system operating parameters on both the average droplet diameter and droplet uniformity were discussed. In addition, a multiple (W/O/W) emulsion formulation was investigated as well.
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Polycaprolactone multicore-matrix particle for the simultaneous encapsulation of hydrophilic and hydrophobic compounds produced by membrane emulsification
Imbrogno, A, Dragosavac, MM, Piacentini, E, Vladisavljevic, GT, Holdich, RG, Giorno, L (2015) Polycaprolactone multicore-matrix particle for the simultaneous encapsulation of hydrophilic and hydrophobic compounds produced by membrane emulsification
COLLOIDS AND SURFACES B-BIOINTERFACES, 135, pp.116-125, DOI |
ABSTRACT: Co-encapsulation of drugs in the same carrier, as well as the development of microencapsulation processes for biomolecules using mild operating conditions, and the production of particles with tailored size and uniformity are major challenges for encapsulation technologies. In the present work, a suitable method consisting of the combination of membrane emulsification with solvent diffusion is reported for the production of multi-core matrix particles with tailored size and potential application in multi-therapies. In the emulsification step, the production of a W/O/W emulsion was carried out using a batch Dispersion Cell for formulation testing and subsequently a continuous azimuthally oscillating membrane emulsification system for the scaling-up of the process to higher capacities. In both cases precise and gentle control of droplet size and uniformity of the W/O/W emulsion was achieved, preserving the encapsulation of the drug model within the droplet. Multi-core matrix particles were produced in a post emulsification step using solvent diffusion. The compartmentalized structure of the multicore-matrix particle combined with the different chemical properties of polycaprolactone (matrix material) and fish gelatin (core material) was tested for the simultaneous encapsulation of hydrophilic (copper ions) and hydrophobic (α-tocopherol) test components. The best operating conditions for the solidification of the particles to achieve the highest encapsulation efficiency of copper ions and α-tocopherol of 99 (±4)% and 93(±6)% respectively were found. The multi-core matrix particle produced in this work demonstrates good potential as a co-loaded delivery system.
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Azimuthally Oscillating Membrane Emulsification for Controlled Droplet Production
Silva, PS, Dragosavac, MM, Vladisavljevic, GT, Bandulasena, HCH, Holdich, RG, Stillwell, M, Williams, B (2015) Azimuthally Oscillating Membrane Emulsification for Controlled Droplet Production AICHE JOURNAL, 61(11), pp.3607-3615, DOI: 10.1002/aic.14894.
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ABSTRACT: A novel membrane emulsification (ME) system is reported consisting of a tubular metal membrane, periodically azimuthally (tangentially) oscillated with frequencies up to 50 Hz and 7 mm displacement in a gently cross flowing continuous phase. A computational fluid dynamics (CFD) analysis showed consistent axial shear at the membrane surface, which became negligible at distances from the membrane surface greater than 0.5 mm. For comparison, CFD analysis of a fully rotating ME system showed local vortices in the continuous phase leading to a variable shear along the axis of the membrane. Using an azimuthally oscillating membrane, oil-in-water emulsions were experimentally produced with a median diameter of 20–120 μm, and a coefficient of variation of droplet size of 8%. The drop size was correlated with shear stress at the membrane surface using a force balance. In a single pass of continuous phase, it was possible to achieve high dispersed phase concentrations of 40% v/v. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3607–3615, 2015
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Controlled production of eco-friendly emulsions using direct and premix membrane emulsification
Santos, J, Vladisavljevic, GT, Holdich, RG, Dragosavac, MM, Munoz, J (2015) Controlled production of eco-friendly emulsions using direct and premix membrane emulsification, CHEMICAL ENGINEERING RESEARCH & DESIGN, 98, pp.59-69, ISSN: 0263-8762. DOI: 10.1016/j.cherd.2015.04.009.
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ABSTRACT: Eco-friendly O/W emulsions were produced by membrane emulsification using nickel membrane consisting of hexagonal arrays of cylindrical pores of 10 or 20 μm diameter and 200 μm spacing. The dispersed phase was a mixture of N,N-dimethyldecanamide (AMD-10TM) and d-limonene containing 0–35 wt% AMD-10TM in the dispersed phase and the continuous aqueous phase was 3 wt% polyoxyethylene glycerol fatty acid ester (Levenol® C-201). In direct membrane emulsification, the droplet-to-pore size ratio was 1.5–4.6 and the most uniform droplets were obtained with pure d-limonene at a stirrer speed of 620 rpm, corresponding to the peak shear stress on the membrane surface of 7 Pa. In premix membrane emulsification, the median droplet diameter decreased with increasing the transmembrane flux and was smaller than the pore size at the flux above 2000 L m−2 h−1. The droplet size was 6 μm after two passes through the membrane with a pore diameter of either 10 or 20 μm. The viscosity of emulsions with 30 wt% was not influenced by the shear rate but an emulsion with a dispersed phase content of 40 wt% showed shear thinning behaviour and viscoelastic properties. The produced emulsions can be used as environmentally friendly matrices for incorporation of agrochemical actives.
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Production of food-grade multiple emulsions with high encapsulation yield using oscillating membrane emulsification
Vladisavljevic, GT, Wang, B, Dragosavac, MM, Holdich, RG (2014) Production of food-grade multiple emulsions with high encapsulation yield using oscillating membrane emulsification, COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 458, pp.78-84, DOI: 10.1016/j.colsurfa.2014.05.011.
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ABSTRACT: Food-grade water-in-oil-in-water (W/O/W) multiple emulsions with a volume median diameter of outer droplets of 50–210 μm were produced by injecting a water-in-oil (W/O) emulsion at the flux of 30 L m−2 h−1 through a 10-μm pore electroplated nickel membrane oscillating at 10–90 Hz frequency and 0.1–5 mm amplitude in 2 wt% aqueous Tween® 20 (polyoxyethylene sorbitan monolaurate) solution. The oil phase in the primary W/O emulsion was 5 wt% PGPR (polyglycerol polyricinoleate) dissolved in sunflower oil and the content of water phase in the W/O emulsion was 30 vol%. The size of outer droplets was precisely controlled by the amplitude and frequency of membrane oscillation. Only 3–5% of the inner droplets with a mean diameter of 0.54 μm were released into the outer aqueous phase during membrane emulsification. A sustained release of 200 ppm copper (II) loaded in the inner aqueous phase was investigated over 7 days. 95% of Cu(II) initially present in the inner water phase was released in the first 2 days from 56-μm diameter multiple emulsion droplets and less than 15% of Cu(II) was released over the same interval from 122 μm droplets. The release rate of Cu(II) decreased with increasing the size of outer droplets and followed non-zero-order kinetics with a release exponent of 0.3–0.5. The prepared multiple emulsions can be used for controlled release of hydrophilic actives in the pharmaceutical, food, and cosmetic industry.
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Production of liposomes using microengineered membrane and co-flow microfluidic device
Vladisavljević, GT, Laouini, A, Charcosset, C, Fessi, H, Bandulasena, HCH, Holdich, RG (2014) Production of liposomes using microengineered membrane and co-flow microfluidic device, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 458(1), pp.168-177, ISSN: 0927-7757. DOI: 10.1016/j.colsurfa.2014.03.016.
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ABSTRACT: Two modified ethanol injection methods have been used to produce Lipoid® E80 and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) liposomes: (i) injection of the organic phase through a microengineered nickel membrane kept under controlled shear conditions and (ii) injection of the organic phase through a tapered-end glass capillary into co-flowing aqueous stream using coaxial assemblies of glass capillaries. The organic phase was composed of 20 mg ml−1 of phospholipids and 5 mg ml−1 of cholesterol dissolved in ethanol and the aqueous phase was ultra-pure water. Self-assembly of phospholipid molecules into multiple concentric bilayers via phospolipid bilayered fragments was initiated by interpenetration of the two miscible solvents. The mean vesicle size in the membrane method was 80 ± 3 nm and consistent across all of the devices (stirred cell, cross-flow module and oscillating membrane system), indicating that local or temporal variations of the shear stress on the membrane surface had no effect on the vesicle size, on the condition that a maximum shear stress was kept constant. The mean vesicle size in co-flow microfludic device decreased from 131 to 73 nm when the orifice diameter in the injection capillary was reduced from 209 to 42 μm at the aqueous and organic phase flow rate of 25 and 5.55 ml h−1, respectively. The vesicle size was significantly affected by the mixing efficiency, which was controlled by the orifice size and liquid flow rates. The smallest vesicle size was obtained under conditions that promote the highest mixing rate. Computational Fluid Dynamics (CFD) simulations were performed to study the mixing process in the vicinity of the orifice.
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Membrane emulsification for the production of uniform poly-N-isopropylacrylamide-coated alginate particles using internal gelation
Hanga, MP and Holdich, RG (2014) Membrane emulsification for the production of uniform poly-N-isopropylacrylamide-coated alginate particles using internal gelation, Chemical Engineering Research and Design, 92(9), pp.1664-1673, DOI: 10.1016/j.cherd.2013.12.010.
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ABSTRACT: Alginate particles, crosslinked by calcium ions, have a number of potential biopharmaceutical industry applications due to the biocompatibility of the materials used and formed. One such use is as microcarriers for cell attachment, growth and then detachment without the use of proteolytic enzymes. A straightforward and reproducible method for producing uniform calcium alginate particles with controllable median diameters which employs membrane emulsification and internal gelation (solid particles contained in the dispersed phase) is demonstrated, as well as functionalisation of the resulting beads with amine terminated poly N-isopropylacrylamide (pNIPAM) to form temperature responsive particles, by taking advantage of the electrostatic interaction between the carboxyl groups of the alginate and amino groups of the modified pNIPAM. Cell attachment, growth and detachment capabilities of these core–shell structures were assessed and successfully demonstrated by using phase contrast microscopy and fluorescent staining with calcein-AM and ethidium homodimer-1.
The formulation used for the alginate particles avoided non-GRAS chemicals by only using food grade and pharmaceutical grade reagents. The median particle size was controllable within the range between 55 μm and 690 μm and the size distributions produced were very narrow: ‘span’ values as low as 0.2. When using a membrane pore size of 20 μm no membrane blockage by the suspended calcium carbonate necessary for internal gelation of the alginate particles was observed. Membrane pore openings with diameters of 5 and 10 μm were also tested, but blocked with the 2.3 μm median diameter calcium carbonate solids. |
Preparation of liposomes: a novel application of microengineered membranes: From laboratory scale to large scale
Laouini, A, Charcosset, C, Fessi, H, Holdich, RG, Vladisavljevic, GT (2013) Preparation of liposomes: a novel application of microengineered membranes: From laboratory scale to large scale, Colloids and Surfaces B: Biointerfaces, 112, pp.272-278, DOI: 10.1016/j.colsurfb.2013.07.066.
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ABSTRACT: A novel ethanol injection method using microengineered nickel membrane was employed to produce POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and Lipoid® E80 liposomes at different production scales. A stirred cell device was used to produce 73 ml of the liposomal suspension and the product volume was then increased by a factor of 8 at the same transmembrane flux (140 l m−2 h−1), volume ratio of the aqueous to organic phase (4.5) and peak shear stress on the membrane surface (2.7 Pa). Two different strategies for shear control on the membrane surface have been used in the scaled-up versions of the process: a cross flow recirculation of the aqueous phase across the membrane surface and low frequency oscillation of the membrane surface (∼40 Hz) in a direction normal to the flow of the injected organic phase. Using the same membrane with a pore size of 5 μm and pore spacing of 200 μm in all devices, the size of the POPC liposomes produced in all three membrane systems was highly consistent (80–86 nm) and the coefficient of variation ranged between 26 and 36%. The smallest and most uniform liposomal nanoparticles were produced in a novel oscillating membrane system. The mean vesicle size increased with increasing the pore size of the membrane and the injection time. An increase in the vesicle size over time was caused by deposition of newly formed phospholipid fragments onto the surface of the vesicles already formed in the suspension and this increase was most pronounced for the cross flow system, due to long recirculation time. The final vesicle size in all membrane systems was suitable for their use as drug carriers in pharmaceutical formulations.
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pH-Sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method
Laouini, A, Koutroumanis, KP, Charcosset, C, Georgiadou, S, Fessi, H, Holdich, RG, Vladisavljevic, GT (2013) pH-Sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method, ACS Applied Materials and Interfaces, 5(18), pp.8939-8947, DOI: 10.1021/am4018237.
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ABSTRACT: A novel membrane contactor method was used to produce size-controlled poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of diblock copolymers with different average molecular weights, Mn (9200 or 10 400 Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m–2 h–1 of the organic phase (a 1 mg mL–1 solution of PEG-PCL in tetrahydrofuran) through a microengineered nickel membrane with a hexagonal pore array and 200 μm pore spacing into deionized water agitated at 700 rpm, the micelle size linearly increased from 92 nm for a 5-μm pore size to 165 nm for a 40-μm pore size. The micelle size was finely tuned by the agitation rate, transmembrane flux and aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug loading of ∼75% (w/w) were achieved when a hydrophobic drug (vitamin E) was entrapped within the micelles, as determined by ultracentrifugation method. The drug-loaded micelles had a mean size of 146 ± 7 nm, a polydispersity index of 0.09 ± 0.01, and a ζ potential of −19.5 ± 0.2 mV. When drug-loaded micelles where stored for 50 h, a pH sensitive drug release was achieved and a maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH-sensitive hydrazone bond was incorporated between PEG and PCL blocks, no significant change in micelle size was observed at the same micellization conditions.
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Microencapsulation of oil droplets using cold water fish gelatine/gum arabic complex coacervation by membrane emulsificationPiacentin, E, Giorno, L, Dragosavac, MM, Vladisavljevic, GT, Holdich, RG (2013) Microencapsulation of oil droplets using cold water fish gelatine/gum arabic complex coacervation by membrane emulsification, Food Research International, 53(1), pp.362-372, DOI: 10.1016/j.foodres.2013.04.012.
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ABSTRACT: Food grade sunflower oil was microencapsulated using cold water fish gelatine (FG)–gum arabic (GA) complex coacervation in combination with a batch stirred cell or continuous pulsed flow membrane emulsification system. Oil droplets with a controllable median size of 40–240 μm and a particle span as low as 0.46 were generated using a microengineered membrane with a pore size of 10 μm and a pore spacing of 200 μm at the shear stress of 1.3–24 Pa. A biopolymer shell around the oil droplets was formed under room temperature conditions at pH 2.7–4.5 and a total biopolymer concentration lower than 4% w/w using weight ratios of FG to GA from 40:60 to 80:20. The maximum coacervate yield was achieved at pH 3.5 and a weight ratio of FG to GA of 50:50. The liquid biopolymer coating around the droplets was crosslinked with glutaraldehyde (GTA) to form a solid shell. A minimum concentration of GTA of 1.4 M was necessary to promote the crosslinking reaction between FG and GTA and the optimal GTA concentration was 24 M. The developed method allows a continuous production of complex coacervate microcapsules of controlled size, under mild shear stress conditions, using considerably less energy when compared to alternative gelatine types and production methods.
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Continuous membrane emulsification with pulsed (oscillatory) flowHoldich, RG, Dragosavac, MM, Vladisavljević, GT, Piacentini, E (2013) Continuous membrane emulsification with pulsed (oscillatory) flow, Industrial and Engineering Chemistry Research, 52(1), pp.507-515, ISSN: 0888-5885. DOI: 10.1021/ie3020457.
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ABSTRACT: Tubular micrometer pore sized sieve type membranes with internal diameter of 14 mm and length of 60 mm containing uniform pores of diameter 10 and 20 μm were used to generate emulsions of sunflower oil dispersed in water and stabilized by Tween 20 using oscillatory flow of the continuous phase. Drop diameters between 30 and 300 μm could be produced, in a controllable way and with span values of down to 0.4. By using pulsed flow it was possible to provide dispersed phase concentrations of up to 45% v/v in a single pass over the membrane, that is, without the need to recirculate the continuous phase through the membrane tube. It was possible to correlate the drop size produced with the shear conditions at the membrane surface using the wave shear stress equation. The oscillatory Reynolds number indicated flow varying from laminar to substantially turbulent, but the change in flow conditions did not show a notable influence on the drop diameters produced, over what is predicted by the varying wall shear stress applied to the wave equation. However, the 20 μm pore sized sieve type membrane appeared to allow the passage of the pressure pulse through the membrane pores, under certain operating conditions, which did lead to finer drop sizes produced than would be predicted. These through-membrane pulsations could be suppressed by changes in operating conditions: a higher dispersed phase injection rate or more viscous continuous phase, and they did not occur under similar operating conditions used with the 10 μm pore sized sieve type of membrane. Generating emulsions of this size using pulsed continuous phase flow provides opportunities for combining drop generation at high dispersed phase concentration, by membrane emulsification, with downstream processing such as reaction in plug flow reactors.
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